Key result
Intrathecal trehalose reduces spinal MMP-2 and MMP-9 expression and accelerates motor recovery after SCI.
Why the study?
Upregulation of MMP-2 and MMP-9 contributes to the secondary pathogenesis of spinal cord injury via inflammation, and although trehalose suppresses post-SCI inflammatory responses, its effect on MMP-2 and MMP-9 expression was unknown.
Hypothesis-generating for low-dose trehalose in rat SCI; leaves open clinical translation.
Upregulation of matrix metalloproteinases (MMPs), in particular MMP-2 and MMP-9 contributes to secondary pathogenesis of spinal cord injury (SCI) via promoting inflammation. Recently, we have reported that trehalose suppresses inflammatory responses following SCI. Therefore, we investigated the effect of trehalose on MMP-2 and MMP-9 expression in SCI. A weight-drop contusion SCI was induced in male rats. Then, the animals received trehalose at three doses of 10 (T10), 100 (T100) and 1000 (T1000) mM intrathecally. MMP-2 and MMP-9 transcripts were then measured in damaged spinal cord at 1, 3 and 7 days after trauma, and compared with vehicle and sham groups. Additionally, behavioral analysis was conducted for 1 week using Basso-Beattie-Bresnahan (BBB) locomotor rating scale. Our data showed an early upregulation of MMP-9 at 1 day post-SCI. However, MMP-2 expression was increased at 3 days after trauma. Treatment with 10 mM trehalose significantly reduced MMP-2 expression in 3 and 7 days (P< 0.01) and MMP-9 expression in 1, 3, and 7 days (P< 0.05) post-damage compared with vehicle. Nonetheless, downregulation of both MMPs was not observed in T100 and T1000 groups. In addition, T10 group showed more rapid recovery of hind limb strength compared with T100 and T1000 groups. We propose that the neuroprotective effect of low dose trehalose is mediated by attenuation of MMP-2 and MMP-9 expression.
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Mirzaie et al. (2018) studied Spinal cord injury (SCI). Intrathecal trehalose vs. Vehicle and sham groups was evaluated on MMP-2 and MMP-9 transcript expression and Basso-Beattie-Bresnahan (BBB) locomotor rating scale (p=<0.01 for MMP-2; <0.05 for MMP-9 (10 mM vs vehicle)). Intrathecal trehalose at 10 mM significantly reduced spinal cord MMP-2 (P<0.01) and MMP-9 (P<0.05) expression and accelerated hind limb recovery compared with vehicle in rats with SCI.
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